*Managed by Martin Marietta Energy Systems, Inc., for
the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

EXECUTIVE SUMMARY

The soluble salts of barium, an alkaline earth metal,
are toxic in mammalian systems. They are absorbed rapidly from the gastrointestinal
tract and are deposited in the muscles, lungs, and bone. Barium is excreted
primarily in the feces.

At low doses, barium acts as a muscle stimulant and at
higher doses affects the nervous system eventually leading to paralysis.
Acute and subchronic oral doses of barium cause vomiting and diarrhea,
followed by decreased heart rate and elevated blood pressure. Higher doses
result in cardiac irregularities, weakness, tremors, anxiety, and dyspnea.
A drop in serum potassium may account for some of the symptoms. Death can
occur from cardiac and respiratory failure. Acute doses around 0.8 grams
can be fatal to humans.

Subchronic and chronic oral or inhalation exposure primarily
affects the cardiovascular system resulting in elevated blood pressure.
A lowest-observed-adverse-effect level (LOAEL) of 0.51 mg barium/kg/day
based on increased blood pressure was observed in chronic oral rat studies
(Perry et al. 1983), whereas human studies identified a no-observed-adverse-effect
level (NOAEL) of 0.21 mg barium/kg/day (Wones et al. 1990, Brenniman and
Levy 1984). The human data were used by the EPA to calculate a chronic
and subchronic oral reference dose (RfD) of 0.07 mg/kg/day (EPA 1995a,b).
In the Wones et al. study, human volunteers were given barium up to 10
mg/L in drinking water for 10 weeks. No clinically significant effects
were observed. An epidemiological study was conducted by Brenniman and
Levy in which human populations ingesting 2 to 10 mg/L of barium in drinking
water were compared to a population ingesting 0 to 0.2 mg/L. No significant
individual differences were seen; however, a significantly higher mortality
rate from all combined cardiovascular diseases was observed with the higher
barium level in the 65+ age group. The average barium concentration was
7.3 mg/L, which corresponds to a dose of 0.20 mg/kg/day. Confidence in
the oral RfD is rated medium by the EPA.

Subchronic and chronic inhalation exposure of human populations
to barium-containing dust can result in a benign pneumoconiosis called
"baritosis." This condition is often accompanied by an elevated
blood pressure but does not result in a change in pulmonary function. Exposure
to an air concentration of 5.2 mg barium carbonate/m3 for 4 hours/day for
6 months has been reported to result in elevated blood pressure and decreased
body weight gain in rats (Tarasenko et al. 1977). Reproduction and developmental
effects were also observed. Increased fetal mortality was seen after untreated
females were mated with males exposed to 5.2 mg/m3 of barium carbonate.
Similar results were obtained with female rats treated with 13.4 mg barium
carbonate/m3. The NOAEL for developmental effects was 1.15 mg/m3 (equivalent
to 0.8 mg barium/m3). An inhalation reference concentration (RfC) of 0.005
mg/m3 for subchronic and 0.0005 mg/m3 for chronic exposure was calculated
by the EPA based on the NOAEL for developmental effects (EPA 1995a). These
effects have not been substantiated in humans or other animal systems.

Barium has not been evaluated by the EPA for evidence
of human carcinogenic potential (EPA 1995b).

1. INTRODUCTION

Barium (CAS registry number 7440-39-3) is a divalent
alkaline-earth metal found only in combination with other elements in nature.
The most important of these combinations are the peroxide, chloride, sulfate,
carbonate, nitrate, and chlorate. The pure metal oxidizes readily and reacts
with water emitting hydrogen; it is chemically similar to calcium (Weast
et al. 1987). The most likely source of barium in the atmosphere is from
industrial emissions. Since it is usually present as a particulate form,
it can be removed from the atmosphere by wet precipitation and deposition.
Due to the element's tendency to form salts with limited solubility in
soil and water, it is expected to have a residence time of hundreds of
years and is not expected to be very mobile. Acidic conditions, however,
will increase the solubility of some barium compounds facilitating their
movement from the soil to the groundwater (EPA 1984). Trace amounts of
barium were found in more than 99% of the surface waters and finished drinking
water samples (average values of 43 g/L, and 28.6 g/L, respectively) across
the United States (National Academy of Sciences 1977).

2. METABOLISM AND DISPOSITION

2.1 ABSORPTION

The soluble forms of barium salts are rapidly absorbed
into the blood from the intestinal tract. The rates of absorption of a
number of barium salts have been measured in rats following oral exposure
to small quantities (30 mg/kg body weight). The relative absorption rates
were found to be: barium chloride barium sulfate barium carbonate. Large
doses of barium sulfate do not increase the uptake of this salt because
of its low solubility (McCauley and Washington 1983, EPA 1984).

Systemic toxic effects have been observed following both
oral and inhalation exposure. No absorption kinetics are available following
inhalation exposure, although it is obvious that absorption does occur
(EPA 1984).

2.2 DISTRIBUTION

Barium absorbed into the bloodstream disappears in about
24 hours; however, it is deposited in the muscles, lungs, and bone. Very
little is stored in the kidneys, liver, spleen, brain, heart, or hair.
It remains in the muscles about 30 hours after which the concentration
decreases slowly. The deposition of barium into bone is similar to calcium
but occurs at a faster rate (Beliles 1994). The half life of barium in
bone is estimated to be about 50 days (Machata 1988).

2.3 METABOLISM

About 54% of the barium dose is protein bound. Barium
is known to activate the secretion of catecholamines from the adrenal medulla
without prior calcium deprivation. It may displace calcium from the cell
membranes, thereby increasing permeability and providing stimulation to
muscles. Eventual paralysis of the central nervous system can occur (Beliles
1994).

2.4 EXCRETION

A tracer study in rats using 140Ba demonstrated that
7% and 20% of the barium dose was excreted in 24 hours in the urine and
feces, respectively. In contrast, calcium is primarily excreted in the
urine. The clearance of barium is enhanced with saline infusion (Beliles
1994). Following intravenous injection of barium into six healthy men,
excretion was mainly fecal with the total relative fecal:urinary clearance
for 14 days ranging from 6 to 15 (Newton et al. 1991).

3. NONCARCINOGENIC HEALTH EFFECTS

3.1 ORAL EXPOSURES

3.1.1 Acute Toxicity

3.1.1.1 Human

A number of accidental barium poisonings have occurred
following the ingestion of barium salts. The estimated fatal dose of barium
carbonate, a rodenticide, is about 5 grams for a 70 kg human (Arena 1979).
The LD50 for barium chloride is estimated at about 1 gram for a 70 kg human
(Machata 1988), and the LDLo (lowest published lethal dose) is reported
to be about 0.8 grams (Lewis and Sweet 1984). The acute symptoms include
excess salivation, vomiting, diarrhea, increased blood pressure, muscular
tremors, weakness, paresis, anxiety, dyspnea, and cardiac irregularities.
A severe loss of potassium can account for some of the symptoms. Convulsions
and death from cardiac and respiratory failure can occur. Magnesium and
sodium sulfate are antidotal if taken soon after ingestion since either
salt will result in the formation of insoluble barium sulfate and prevent
further absorption. Survival for more than 24 hours is usually followed
by complete recovery (Arena 1979).

Complications occurred in a woman following a barium
swallow investigation for severe dysphagia. Direct aspiration of a large
amount of barium into the right main bronchus resulted in tachycardia,
tachypnoea, fever, and an oxygen saturation of 82%; two weeks later the
woman still had a moist cough with widespread rales but continued to recover
(Penington 1993).

A family was accidentally poisoned with barium from eating
their evening meal. The mother had fried fish breaded with a flour-like
substance that turned out to be rat poison containing barium carbonate.
All seven family members, aged 2 to 48 years, developed nausea, vomiting,
diarrhea, and crampy abdominal pain within minutes of consuming the meal;
the parents also developed ventricular tachycardia, flaccid paralysis of
the extremities, shortness of breath (mother), and respiratory failure
(father). Patients were treated symptomatically and all fully recovered
(Johnson and VanTassell 1991).

3.1.1.2 Animal

Similar acute symptoms occur in animals; however, higher
doses are usually involved. The LD50 for rats is listed as 630 mg/kg for
barium carbonate, 118 mg/kg for barium chloride, and 921 mg/kg for barium
acetate (Lewis and Sweet 1984).

3.1.2 Subchronic Toxicity

3.1.2.1 Human

An experiment testing the subchronic toxicity of barium
chloride on human volunteers was conducted by Wones et al. (1990). The
diets of 11 male subjects were controlled. They were given 1.5 L/day of
distilled and charcoal-filtered drinking water that contained 0 mg/L barium
for weeks 1 and 2, 5 mg/L for weeks 3 to 6, and 10 mg/L for weeks 7 to
10. No clinically significant effects were observed in blood pressures,
serum chemistry, urinalysis, or electrocardiograms. The 10 mg/L (0.21 mg/kg/day)
dose was identified as a NOAEL.

3.1.2.2 Animal

Groups of 30 male and 30 female Charles River rats were
exposed to barium chloride at 0, 10, 50, or 250 ppm in drinking water for
90 days (Tardiff et al. 1980). The highest average dose in this study was
calculated to be 45.7 mg/kg/day for female rats. No significant clinical
signs of toxicity were observed. Blood pressure was not measured.

McCauley et al. (1985) conducted drinking water studies
in which six male Sprague-Dawley rats/group were given water containing
0, 10, 100, or 250 mg/L barium for 36 weeks, or 1, 10, 100, or 1000 mg/L
barium for 16 weeks. Female rats were given 0 or 250 mg/L for 46 weeks.
Animals receiving the 1000 mg/L dose developed ultrastructural changes
in the kidney glomeruli. No other effects were reported.

Tardiff et al. (1980) exposed groups of 30 male and 30
female Charles River rats to 0, 10, 50, or 250 ppm barium (given as barium
chloride) in drinking water for 90 days. A slight reduction in adrenal
weights was seen in female rats with the 250 ppm (45.7 mg/kg/day) dose
at 13 weeks, and no other adverse effects were observed in male rats with
the 50 ppm (8.1 mg/kg/day) and the 250 ppm (38.1 mg/kg/day) doses at 8
weeks. No clear dose effect or dose duration effect was seen with the adrenal
weight decrease; therefore, the clinical significance is uncertain.

3.1.3 Chronic Toxicity

3.1.3.1 Human

An epidemiology study conducted by Brenniman and Levy
(1984) compared a human population ingesting barium levels of 2 to 10 mg/L
in their drinking water to a population ingesting 0 to 0.2 mg/L. Although
significantly higher mortality rates from all cardiovascular diseases were
observed with the higher barium level in the 65 and over age group, there
were no significant individual differences in blood pressures, strokes,
or heart and renal diseases within the two groups. The average barium concentration
for the mortality study was 7.3 mg/L, which corresponds to a dose of 0.20
mg/kg/day assuming drinking water consumption of 2 L/day for a 70 kg human.

3.1.3.2 Animal

A series of experiments were performed in which groups
of 52 male and female Long-Evans rats and 42 male and female Swiss mice
were exposed to 5 mg barium/L (given as barium acetate) in drinking water
for their lifetime (Schroeder and Mitchener 1975a,b). The barium doses
were about 0.25 and 0.825 mg/kg/day for rats and mice, respectively. No
adverse clinical effects were observed; however, blood pressure was not
measured. A slight but significant reduction in longevity of treated male
mice was noted when measured as the mean age at death of the last surviving
10% of animals. The overall average life span of the group, however, was
about the same as the control group (EPA 1984, 1989).

Perry et al. (1983) exposed 12 to 13 female weanling
rats/group to 0, 1, 10, or 100 ppm barium (given as barium chloride) for
up to 16 months. Average doses were calculated to be 0, 0.051, 0.51, and
5.1 mg/kg/day (EPA 1985). A clinically significant increase in average
blood pressure was observed in the highest dose group; a slight but statistically
significant increase was seen in the 10 ppm (0.51 mg/kg/day) dose group.
The controlled diet, which restricted the intake of trace metals, calcium,
and potassium, may have contributed to the effect.

3.1.4 Developmental and Reproductive Toxicity

Information on developmental and reproductive toxicity
in humans or

animals following oral exposure was unavailable.

3.1.5 Reference Dose

3.1.5.1 Subchronic

ORAL RfDs: 0.07 mg/kg/day (EPA 1995a)

UNCERTAINTY FACTOR: 3

NOAEL: 0.21 mg/kg/day

PRINCIPAL STUDIES: The same studies and comments apply
to both the

subchronic and chronic RfD derivations. See Sect. 3.1.5.2.

3.1.5.2 Chronic

ORAL RfDc: 0.07 mg/kg/day (EPA 1995b)

UNCERTAINTY FACTOR: 3

MODIFYING FACTOR: 1

NOAEL: 0.21 mg/kg/day

CONFIDENCE:

Study: Medium

Data Base: Medium

RfD: Medium

VERIFICATION DATE: 06/21/90

PRINCIPAL STUDIES: Wones et al. (1990); Brenniman and
Levy (1984).

COMMENTS: The RfD values are based on a weight-of-evidence
approach using subchronic to chronic human drinking water studies. The
uncertainty factor accounts for protecting sensitive individuals and is
reduced from the usual factor of 10 because the selected studies examined
the population judged most at risk.

3.2 INHALATION EXPOSURES

3.2.1 Acute Toxicity

3.2.1.1 Human

Barium carbonate dust has been reported to be a bronchial
irritant. Barium oxide dust is considered a dermal and nasal irritant (Beliles
1994). The effect of barium dusts on welders was investigated under simulated
working conditions over a one-week time period (Zschiesche et al. 1992).
Barium fume concentrations were 4.4 and 2.0 mg/m3 during welding with stick
electrodes and flux cored wires, respectively. No adverse health effects
on the welders were attributable to barium exposure, but there was a slight
decrease in plasma potassium levels at the end of the work shift.

3.2.1.2 Animal

Information on the acute inhalation toxicity of barium
in animals

was not available.

3.2.2 Subchronic Toxicity

3.2.2.1 Human

Industrial workers exposed to barium dust, usually in
the form of barium sulfate or carbonate, often develop a benign pneumoconiosis
referred to as "baritosis." Because of the radiopacity of barium
compounds, this condition can be specifically diagnosed radiologically.
After removal from the sources of exposure, baritosis is reversible in
most cases. Baritosis results in a significantly higher incidence of hypertension,
but no changes are usually seen in pulmonary function (Stokinger 1981,
EPA 1995b).

Information on the chronic inhalation toxicity of barium
in animals was not available.

3.2.4 Developmental and Reproductive Toxicity

Tarasenko et al. (1977) performed a series of experiments
in rats designed to test for possible reproductive and developmental effects.
Increased fetal mortality was observed following the mating of males exposed
to barium carbonate (5.2 mg/m3 air) with untreated females. Decreased sperm
motility was observed in males treated with 22.6 mg/m3. The mating of females
exposed to 13.4 mg/m3 for 4 months also resulted in increased fetal mortality
and a general under development of the newborn pups. Ovarian follicle atresia
was seen in female rats exposed to 3.1 mg/m3. No significant adverse effects
were noted with the 1.15 mg/m3 concentration (EPA 1984).

3.2.5 Reference Concentration/Dose

3.2.5.1 Subchronic

INHALATION RfCs: 0.005 mg/m3; 0.001 mg/kg/day (EPA 1995a)

UNCERTAINTY FACTOR: 100

NOEL: 0.8 mg Ba/m3 given 4 hr/day (EPA 1995a)

PRINCIPAL STUDY: The same study and comments apply to
the subchronic

and chronic RfC. The study is described in Sect. 3.2.4.

3.2.5.2 Chronic

INHALATION RfCc: 0.0005 mg/m3; 0.0001 mg/kg/day (EPA
1995a)

UNCERTAINTY FACTOR: 1000

NOEL: 0.8 mg Ba/m3 given 4 hr/day (EPA 1995a)

PRINCIPAL STUDY: Tarasenko et al. 1977

COMMENTS: The dose of 1.15 mg BaCO3/m3 was given as the
NOEL in the principal study, which is equivalent to 0.8 mg barium/m3 used
as the basis for the RfC calculations. An inhalation risk assessment for
barium is under review by an EPA work group (EPA, 1995b).